Polysiloxanes are applied in many ways in industry e.g. as surfactants, coatings, dispersion agents, dispersion stabilisers, release agents, food additives, sealants, tubes and medical applications. Polysiloxanes are also applied in many ways in medical industry, e.g. in drug delivery applications, both as coatings in conventional pills and as implantable, intravaginal or intrauterine devices. The most commonly used polysiloxane is polydimethylsiloxane (PDMS), which is a highly hydrophobic, stable and temperature resistant material. PDMS is especially suitable for use as membranes regulating the release rate of drugs. However, as PDMS is hydrophobic, it cannot be used for all drugs, depending of the hydrophilicity or hydrophobicity of the drug.
However, when preparing polysiloxanes by ring opening polymerisation of cyclic siloxanes with phosphazene base catalysts, a large amount of catalyst is required, leading to cross-linking of the polymers during storage.
Sterically hindered phenols, such as α-tocopherols and their derivatives have been used in the polymerisation reactions to slow down the reaction and to prevent the formation of gels and oligomers. Tocopherol has also been used as a stabiliser in polymers due to its anti-oxidant effect.
There is, however, still a need to provide a co-catalyst suitable for reducing the amount of catalyst used during the ring opening polymerisation of cyclic siloxanes. There is also a need to provide a component capable of strongly reducing, if not completely avoiding, the cross-linking of the polymers thus obtained during storage.
Concerning the medical applications, the release rate of the drug has traditionally been regulated by changing the parameters of the drug release system, for example by changing the surface area, the thickness of the membrane, the quantity of the drug or the amount of fillers in the membrane regulating the release. However, if a significant change of the release rate is desired or if the dimensions of the delivery device cannot be modified, the constitution of the polymer needs to be modified.
It is known that the diffusion properties of polydimethylsiloxane can be varied by adding to the polymer substituent groups that decrease or increase the release rate.
The addition of polyethylene oxide (PEO) groups into PDMS polymer can increase the release rate of drugs. Ullman et al. presents in Journal of Controlled Release 10 (1989) 251-260 membranes made of block copolymer comprising polyethylene oxide and PDMS, and the release of different steroids through these membranes. According to the publication, the release of hydrophilic steroids is increased and the release of lipophilic steroids is decreased, when the amount of PEO groups increases. In that study the PEO groups are connected to the silicon atoms of the siloxane groups via a urea-bond.
Patent Fl 107339 discloses regulating the release rate of drugs by a siloxane-based elastomer composition comprising at least one elastomer and possibly a non-crosslinked polymer, as well as a method for manufacturing said elastomer composition. The elastomer or the polymer of the composition comprises polyalkylene oxide groups as alkoxy-terminated grafts or blocks of the polysiloxane units, or a mixture of these. The alkoxy-terminated grafts or blocks are connected to the siloxane units by silicon-carbon-bonds.
Publication Hu et al. “Synthesis and drug release property of polysiloxane containing pendant long alkyl ether group”, Gaofenzi Xuebao, (1) 6247, 1997 Kexue (CA 126:200090) presents a silicone based polymer that has been grafted with ether groups after the polymerization step, thus leaving the hydrosilation catalyst (Pt) inside the polymer. The polymer is useful when mixed with silicone rubber. The publication only discloses simple ether groups. The polymer grafted as disclosed decreases the release rate of the drugs.
U.S. Pat. No. 6,346,553 discloses alkylmethylsiloxane-polyalkyleneoxide-dimethylsiloxane-copolymers, that are suitable for use as surface-active agent for both oil-water-emulsions and silicone-water-emulsion, and a method for manufacturing said copolymers. The copolymers can be manufactured by a hydrosilylation reaction between a straight chain or branched chain olefin and a cyclic siloxane, using platinum catalyst, distilling the alkylated cyclic siloxane, polymerising the mixture of said tetramethyldisiloxane and possibly another cyclic siloxane in the presence of an acidic catalyst. The obtained polymer is finally hydrosilylated with a terminally unsaturated polyalkyleneoxide polymer.
U.S. Pat. No. 6,294,634 presents a method for manufacturing siloxane compositions by heating a mixture of dimethylsiloxane, alkyl-substituted cyclic siloxane and a cyclic siloxane comprising a oxyalkylene-group, in the absence of solvent. The polymerisation catalyst can be, for example, alkaline metal hydroxide, alkoxide or silanolate, Lewis acids, acidic phosphazenes or basic phosphazenes. The composition comprises only small residues of platinum or is completely free from platinum.
U.S. Pat. No. 3,427,271 discloses organic polysiloxanes that are formed of dimethylsiloxane units, methyl-oxyalkylsiloxane units and siloxane units that are substituted with methyl group and a higher alkyl group. The polymerisation reaction uses platinum catalyst.